Information obtained over the past 25 years indicates that the amino acid glutamate functions as a fast excitatory transmitter in the mammalian brain. Studies completed during the last 15 years have also demonstrated that glutamate is a powerful neurotoxin, capable of killing neurons in the central nervous system when its extracellular concentration is sufficiently high. Recent experiments in a variety of preparations have shown that either blockade of synaptic transmission or the specific antagonism of postsynaptic glutamate receptors greatly diminishes the sensitivity of central neurons to hypoxia and ischemia. These experiments suggest that glutamate plays a key role in ischemic brain damage, and that drugs which decrease the accumulation of glutamate or block its postsynaptic effects may be a rational therapy for stroke.

Glutamate and pathophysiology of hypoxic-ischemic brain damage

Glutamate and the pathophysiology of hypoxic--ischemic brain damage.

Diffusion-weighted MR images were compared with T2-weighted MR images and correlated with 1H spin-echo and 31P MR Spectroscopy for 6-8 h following a unilateral middle cerebral and bilateral carotid artery occlusion in eight cats. Diffusion-weighted images using strong gradient strengths (b values of 1413 s/mm2) displayed a significant relative hyperintensity in ischemic regions as early as 45 min after onset of ischemia whereas T2-weighted spin-echo images failed to clearly demonstrate brain injury up to 2-3 h postocclusion. Signal intensity ratios (SIR) of ischemic to normal tissues were greater in the diffusion-weighted images at all times than in either TE 80 or TE 160 ms T2-weighted MR images. Diffusion- and T2-weighted SIR did not correlate for the first 1-2 h postocclusion. Good correlation was found between diffusion-weighted SIR and ischemic disturbances of energy metabolism as detected by 31P and 1H MR Spectroscopy. Diffusion-weighted hyperintensity in ischemic tissues may be temperature-related, due to rapid accumulation of diffusion-restricted water in the intracellular space (cytotoxic edema) resulting from the breakdown of the transmembrane pump and/or to microscopic brain pulsations. © 1990 Academic Press, Inc.

Early detection of regional cerebral ischemia in cats: comparison of diffusion- and T2-weighted MRI and spectroscopy.

All cells in living organisms have a limited life span, and when the time set by their biological clocks has run out, they will die , their highly orga­ nized macromolec ular structure will disintegrate, and the low-molec ul ar degrad ation products be­ come part of the disorder of the surroundings . In thermodynamic terms, this series of events consti­ tutes what has been c alled the entropic doom. We know little about those molec ul ar mechanisms that limit the life span of cells in the absence of dise ase. For the clinician, therefore, the important task is to prevent or tre at dise ases that jeopardize the proper functioning and viability of cells whose biologic al clocks have not yet run out . Measures instituted to prevent brain cell death have a special importance . This i s partly due t o the fact that w e equate human life with the functioning of the brain. However, this importance also resides in the v ulnerability of brain cells to conditions that allow cells of most other tissue to survive , and to continue or res ume their activitie s . The clinically most important conditions leading to brain cell death are those associated with cere­ brovascul ar dise ase, particularly stroke, and with head trauma. We will begin, though, by rec alling the traditional view of the occ urrence and loc alization of neuronal damage in four conditions that lead to more disseminated alterations, e specially since they have been considered to c ause nerve cell injury of a

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.1981.18

Cell Damage in the Brain: A Speculative Synthesis

Functional Magnetic Resonance Imaging

✓ The incidence and natural history of the cavernous angioma have remained unclear in part because of the difficulty of diagnosing and following this lesion prior to surgical excision. The introduction of magnetic resonance (MR) imaging has improved the sensitivity and specificity of diagnosing and following this vascular malformation. Seventy-six lesions with an MR appearance typical of a presumed cavernous angioma were discovered in 66 patients among 14,035 consecutive MR images performed at the Cleveland Clinic between 1984 and 1989. Follow-up studies in 86% of the cases over a mean period of 26 months provided 143 lesion-years of clinical survey of this condition. The most frequent presenting features were seizure, focal neurological deficit, and headache. While most lesions exhibited evidence of occult bleeding on MR imaging, there was overt hemorrhage in seven of the 57 symptomatic patients and only one overt hemorrhage occurred during the follow-up interval. The annualized bleeding rate was 0.7%. A...

Natural history of the cavernous angioma

The natural history of cranial dural arteriovenous malformations (AVM's) is highly variable. The authors present their clinical experience with 17 dural AVM's in adults, including 10 cases with an aggressive neurological course (strictly defined as hemorrhage or progressive focal neurological deficit other than ophthalmoplegia). Two of these 10 patients died prior to surgical intervention and a third was severely disabled by intracerebral hemorrhage. Six patients underwent surgical resection of their dural AVM, with preparatory embolization in two cases. One patient received embolization and radiation therapy without surgery. Six of the seven cases without an aggressive neurological course were treated conservatively, and the seventh patient underwent embolization of a cavernous sinus dural AVM because of worsening ophthalmoplegia. In order to clarify features associated with aggressive behavior, a comprehensive meta-analysis was performed on 360 additional dural AVM's reported in the literature with sufficiently detailed clinical and angiographic information. The location and angiographic features of 100 aggressive cases were compared to those of 277 benign cases. No location of dural AVM's was immune from aggressive neurological behavior; however, an aggressive neurological course was least often associated with cases involving the transverse-sigmoid sinuses and cavernous sinus and most often associated with cases at the tentorial incisura. Contralateral contribution to arterial supply and rate of shunting (high vs. low flow) did not correlate with aggressive neurological behavior as defined. Leptomeningeal venous drainage, variceal or aneurysmal venous dilations, and galenic drainage correlated significantly (p less than 0.05) with aggressive neurological presentation. The latter three angiographic features often coexisted in the same dural AVM. It is concluded that these features significantly increase the natural risk of dural AVM's, and warrant a more vigilant therapeutic strategy.

Intracranial dural arteriovenous malformations: factors predisposing to an aggressive neurological course

In 29 cases of meningeal carcinomatosis reviewed, the widespread involvement of the cranial and spinal leptomeninges produced a complex neurological picture that made the diagnosis difficult. Examination of cerebrospinal fluid was the most helpful diagnostic procedure; the fluid often had decreased glucose and an increased protein content and contained malignant cells. Diffuse leptomeningeal and craniospinal nerve root infiltration was a consistent postmortem finding. The propensity of adenocarcinoma to metastasize in this fashion is reflected by the high frequency of this histologic type in this series. The two commonest primary sites were the breast and lung. In all patients there was progressive clinical deterioration; the average survival after diagnosis was only six weeks.

Meningeal carcinomatosis. Clinical manifestations.

A series of 4992 intracranial procedures performed over an 11-year period was evaluated for the occurrence of postoperative hemorrhage. Forty patients (0.8%) experienced postoperative hemorrhage. Twenty-four hemorrhages were intracerebral (60%), 11 were epidural (28%), 3 were subdural (7.5%), and 2 were intrasellar (5.0%). Hematomas in 33 patients occurred at the operative site, and 7 occurred remote from the operative site. Intracranial tumor was the reason for operation in 56% of the patients developing a clot, and meningioma was the most common tumor associated with this complication. The use of the sitting position was not associated with an increased incidence of postoperative hemorrhage. Disturbances of coagulation and hypertension seemed to be potential precipitating factors. Postoperative hemorrhage was recognized within 12 hours of operation in 35% of the patients. An altered level of consciousness was the most frequent clinical finding, present in all patients. There was no clear relationship between the time of recognition and the final clinical outcome. Parenchymal clots carried the worst prognosis, accounting for 8 of the 11 deaths and all 7 patients with poor neurological outcome.

Postoperative hemorrhage: a survey of 4992 intracranial procedures.

✓ Thirty-eight cases of colloid cyst of the third ventricle are reviewed. Headache was the most frequent complaint but a strong positional relationship, supposedly a pathognomonic feature of this tumor, was seldom seen. A combination of progressive dementia and gait disturbance without evidence of papilledema, resembling the clinical picture in “normal-pressure” hydrocephalus, was present in eight patients. Sudden deterioration and death occurred in four cases; two other deaths were precipitated by lumbar puncture and pneumoencephalography. Ventriculography was the most reliable diagnostic study. Both the demonstration of dilatation of the lateral ventricles and an upward convexity in the initial segment of the internal cerebral vein in five of the 10 angiograms performed were highly suggestive of tumor. Removal of the colloid cyst through a cortical incision in the non-dominant hemisphere was carried out in 21 cases; in six it was necessary to enlarge the foramen of Monro by dividing the ipsilateral ante...

John R. Little

Papers

Natural history of the cavernous angioma

Intracranial dural arteriovenous malformations: factors predisposing to an aggressive neurological course

Meningeal carcinomatosis. Clinical manifestations.

Postoperative hemorrhage: a survey of 4992 intracranial procedures.

Colloid cysts of the third ventricle